The demonstration that the state of allogeneic unresponsiveness associated with bone marrow chimerism under the conditions of this study is related to a central inhibition of clonal proliferation of antigen-responsive lymphocytes has stimulated renewed interest in the immunological consequences of supralethal total body irradiation. This consideration may be of particular relevance to earlier suggestions that the immediate post-irradiation and bone marrow transplantation phase may constitute a special period of immunological ductility, akin to that which has been documented in the fetal and/or neonatal state in a variety of mammalian species. As demonstrated by the classical studies of Billingham, Brent and Medawar, the fetal and/or neonatal state constitutes periods of immunological receptiveness during which allogeneic unresponsiveness can be induced. Earlier studies in this laboratory have demonstrated that Cooperstown radiation chimeras which were tested withint 3 to 6 months after irradiation and bone marrow transplantation, had been rendered specifically tolerant of other tissues (skin, kidney, heart, liver, pancreas) obtained from the specific donor of marrow. During the forthcoming period of research, an attempt will be made to broaden the individual specific nature of the state of immunological tolerance associated with irradiation and bone marrow transplantation, by variations in the timing of organ transplantation after irradiation. Data obtained on the basis of this approach in the Cooperstown colony donor-recipient pairs of known DL-A DS and LD genotype will be extended peri passu to studies in mongrel dogs. BIBLIOGRAPHIC REFERENCES: Bachvaroff, R., Skupp, S., Vugrek, G., Ayvazian, J.H. and Rapaport, F.T. Lymphocyte differentiation and in vitro histocompatibility. Transpl. Proc. (Suppl. 1), 7:279, 1975. Rapaport, F.T., Lawrence, H.S., Bachvaroff, R., Cannon, F.D., Blumenstock, D., Mollen, N., Ayvazian, J.H. and Ferrebee, J.W. Mechanisms of tolerance in adult dogs: Donor-host interrelationships in the induction of allograft tolerance by supralethal total-body irradiation and bone marrow transplantation. Transpl. Proc. (Suppl. 1), 7:367, 1975.